tbuckley/cabot-search huggingface dataset:
Diagnosis of Heart Failure With Preserved Ejection Fraction Among Patients With Unexplained Dyspnea
Authors: Yogesh N. V. Reddy, David M. Kaye, M. Louis Handoko, Arno A. van de Bovenkamp, Ryan J. Tedford, Carson Keck, Mads J. Andersen, Kavita Sharma, Rishi K. Trivedi, Rickey E. Carter, Masaru Obokata, Frederik H. Verbrugge, Margaret M. Redfield, Barry A. Borlaug
Journal: JAMA Cardiology (2022)

Diagnosis of heart failure with preserved ejection fraction (HFpEF) among dyspneic patients without overt congestion is challenging. Multiple diagnostic approaches have been proposed but are not well validated against the independent gold standard for HFpEF diagnosis of an elevated pulmonary capillary wedge pressure (PCWP) during exercise.To evaluate H2FPEF and HFA-PEFF scores and a PCWP/cardiac output (CO) slope of more than 2 mm Hg/L/min to diagnose HFpEF.This retrospective case-control study included patients with unexplained dyspnea from 6 centers in the US, the Netherlands, Denmark, and Australia from March 2016 to October 2020. Diagnosis of HFpEF (cases) was definitively ascertained by the presence of elevated PCWP during exertion; control individuals were those with normal rest and exercise hemodynamics.Logistic regression was used to evaluate the accuracy of HFA-PEFF and H2FPEF scores to discriminate patients with HFpEF from controls.Among 736 patients, 563 (76%) were diagnosed with HFpEF (mean [SD] age, 69 [11] years; 334 [59%] female) and 173 (24%) represented controls (mean [SD] age, 60 [15] years; 109 [63%] female). H2FPEF and HFA-PEFF scores discriminated patients with HFpEF from controls, but the H2FPEF score had greater area under the curve (0.845; 95% CI, 0.810-0.875) compared with the HFA-PEFF score (0.710; 95% CI, 0.659-0.756) (difference, -0.134; 95% CI, -0.177 to -0.094; P < .001). Specificity was robust for both scores, but sensitivity was poorer for HFA-PEFF, with a false-negative rate of 55% for low-probability scores compared with 25% using the H2FPEF score. Use of the PCWP/CO slope to redefine HFpEF rather than exercise PCWP reclassified 20% (117 of 583) of patients, but patients reclassified from HFpEF to control by this metric had clinical, echocardiographic, and hemodynamic features typical of HFpEF, including elevated resting PCWP in 66% (46 of 70) of reclassified patients.In this case-control study, despite requiring fewer data, the H2FPEF score had superior diagnostic performance compared with the HFA-PEFF score and PCWP/CO slope in the evaluation of unexplained dyspnea and HFpEF in the outpatient setting.
Authors’ reply to Booth and colleagues
Authors: Stephen H Bradley, Garth Funston, Daniel Jones, Jessica Watson
Journal: BMJ (2022)

Campbell et al.’s [2001] influential paper on idiosyncratic volatility has received a lot of research attention in recent years. The critical question for portfolio managers is: “How does idiosyncratic volatility affect stock selection and asset allocation signals?” This article examines that important question. Using well-accepted metrics of idiosyncratic volatility, the authors find that the effectiveness of both the momentum and the valuation signals critically depends on cross-sectional differences in idiosyncratic volatility. In particular, they find that the mean reversion signal works better for firms with low idiosyncratic volatility, whereas the momentum signal works better for those with high idiosyncratic volatility. This result is robust across different regimes of idiosyncratic volatility. Finally, the authors test whether a measure of idiosyncratic volatility has an impact on the Fed Model for asset allocation. They find that conditioning the signal in the Fed Model for cross-sectional differences in idiosyncratic volatility significantly improves the mean reversion effect that underlies the Fed Model. In summary, they note that it is important to condition stock selection and asset allocation models for cross-sectional differences in idiosyncratic volatility. <b>TOPICS:</b>Volatility measures, portfolio theory, security analysis and valuation
Covid-19: MPs call for greater efforts to reach the unvaccinated and partially vaccinated
Authors: Jacqui Wise
Journal: BMJ (2022)

Gene regulatory feedback loops generate autonomous circadian rhythms in mammalian tissues. The well-studied core clock network contains many negative and positive regulations. Multiple feedback loops have been discussed as primary rhythm generators but the design principles of the core clock and differences between tissues are still under debate. Here we use global optimization techniques to fit mathematical models to circadian gene expression profiles for different mammalian tissues. It turns out that for every investigated tissue multiple model parameter sets reproduce the experimental data. We extract for all model versions the most essential feedback loops and find auto-inhibitions of period and cryptochrome genes, <i>Bmal1–Rev-erb-α</i> loops, and repressilator motifs as possible rhythm generators. Interestingly, the essential feedback loops differ between tissues, pointing to specific design principles within the hierarchy of mammalian tissue clocks. Self-inhibitions of <i>Per</i> and <i>Cry</i> genes are characteristic for models of suprachiasmatic nucleus clocks, whereas in liver models many loops act in synergy and are connected by a repressilator motif. Tissue-specific use of a network of co-existing synergistic feedback loops could account for functional differences between organs.
EHA Guidelines on Management of Antithrombotic Treatments in Thrombocytopenic Patients With Cancer
Authors: Anna Falanga, Avi Leader, Chiara Ambaglio, Zsuzsa Bagoly, Giancarlo Castaman, Ismail Elalamy, Ramon Lecumberri, Alexander Niessner, Ingrid Pabinger, Sebastian Szmit, Alice Trinchero, Hugo Ten Cate, Bianca Rocca
Journal: HemaSphere (2022)

In cancer patients, thrombocytopenia can result from bone marrow infiltration or from anticancer medications and represents an important limitation for the use of antithrombotic treatments, including anticoagulant, antiplatelet, and fibrinolytic agents. These drugs are often required for prevention or treatment of cancer-associated thrombosis or for cardioembolic prevention in atrial fibrillation in an increasingly older cancer population. Data indicate that cancer remains an independent risk factor for thrombosis even in case of thrombocytopenia, since mild-to-moderate thrombocytopenia does not protect against arterial or venous thrombosis. In addition, cancer patients are at increased risk of antithrombotic drug-associated bleeding, further complicated by thrombocytopenia and acquired hemostatic defects. Furthermore, some anticancer treatments are associated with increased thrombotic risk and may generate interactions affecting the effectiveness or safety of antithrombotic drugs. In this complex scenario, the European Hematology Association in collaboration with the European Society of Cardiology has produced this scientific document to provide a clinical practice guideline to help clinicians in the management of patients with cancer and thrombocytopenia. The Guidelines focus on adult patients with active cancer and a clear indication for anticoagulation, single or dual antiplatelet therapy, their combination, or reperfusion therapy, who have concurrent thrombocytopenia because of either malignancy or anticancer medications. The level of evidence and the strength of the recommendations were discussed according to a Delphi procedure and graded according to the Oxford Centre for Evidence-Based Medicine.
Targeted Genome Sequencing Identifies Multiple Rare Variants in Caveolin-1 Associated with Obstructive Sleep Apnea
Authors: Jingjing Liang, Heming Wang, Brian E. Cade, Nuzulul Kurniansyah, Karen Y. He, Jiwon Lee, Scott A. Sands, Jennifer A. Brody, Han Chen, Daniel J. Gottlieb, Daniel S. Evans, Xiuqing Guo, Sina A. Gharib, Lauren Hale, David R. Hillman, Pamela L. Lutsey, Sutapa Mukherjee, Heather M. Ochs-Balcom, Lyle J. Palmer, Shaun Purcell, Richa Saxena, Sanjay R. Patel, Katie L. Stone, Gregory J. Tranah, Eric Boerwinkle, Xihong Lin, Yongmei Liu, Bruce M. Psaty, Ramachandran S. Vasan, Ani Manichaikul, Stephen S. Rich, Jerome I. Rotter, Tamar Sofer, Susan Redline, Xiaofeng Zhu
Journal: American Journal of Respiratory and Critical Care Medicine (2022)

Rationale: Obstructive sleep apnea (OSA) is a common disorder associated with increased risk for cardiovascular disease, diabetes, and premature mortality. There is strong clinical and epidemiologic evidence supporting the importance of genetic factors influencing OSA but limited data implicating specific genes. Objectives: To search for rare variants contributing to OSA severity. Methods: Leveraging high-depth genomic sequencing data from the NHLBI Trans-Omics for Precision Medicine (TOPMed) program and imputed genotype data from multiple population-based studies, we performed linkage analysis in the CFS (Cleveland Family Study), followed by multistage gene-based association analyses in independent cohorts for apnea–hypopnea index (AHI) in a total of 7,708 individuals of European ancestry. Measurements and Main Results: Linkage analysis in the CFS identified a suggestive linkage peak on chromosome 7q31 (LOD = 2.31). Gene-based analysis identified 21 noncoding rare variants in CAV1 (Caveolin-1) associated with lower AHI after accounting for multiple comparisons (P = 7.4 × 10−8). These noncoding variants together significantly contributed to the linkage evidence (P < 10−3). Follow-up analysis revealed significant associations between these variants and increased CAV1 expression, and increased CAV1 expression in peripheral monocytes was associated with lower AHI (P = 0.024) and higher minimum overnight oxygen saturation (P = 0.007). Conclusions: Rare variants in CAV1, a membrane-scaffolding protein essential in multiple cellular and metabolic functions, are associated with higher CAV1 gene expression and lower OSA severity, suggesting a novel target for modulating OSA severity.
Excluding Hollow Viscus Injury for Abdominal Seat Belt Sign Using Computed Tomography
Authors: Patrick T. Delaplain, Erika Tay-Lasso, Walter L. Biffl, Kathryn B. Schaffer, Margaret Sundel, Samar Behdin, Mira Ghneim, Todd W. Costantini, Jarrett E. Santorelli, Emily Switzer, Morgan Schellenberg, Jessica A. Keeley, Dennis Y. Kim, Andrew Wang, Navpreet K. Dhillon, Deven Patel, Eric M. Campion, Caitlin K. Robinson, Susan Kartiko, Megan T. Quintana, Jordan M. Estroff, Katharine A. Kirby, Jeffry Nahmias
Journal: JAMA Surgery (2022)

Abdominal seat belt sign (SBS) has historically entailed admission and observation because of the diagnostic limitations of computed tomography (CT) imaging and high rates of hollow viscus injury (HVI). Recent single-institution, observational studies have questioned the utility of this practice.To evaluate whether a negative CT scan can safely predict the absence of HVI in the setting of an abdominal SBS.This prospective, observational cohort study was conducted in 9 level I trauma centers between August 2020 and October 2021 and included adult trauma patients with abdominal SBS.Inclusion in the study required abdominal CT as part of the initial trauma evaluation and before any surgical intervention, if performed. Results of CT scans were considered positive if they revealed any of the following: abdominal wall soft tissue contusion, free fluid, bowel wall thickening, mesenteric stranding, mesenteric hematoma, bowel dilation, pneumatosis, or pneumoperitoneum.Presence of HVI diagnosed at the time of operative intervention.A total of 754 patients with abdominal SBS had an HVI prevalence of 9.2% (n = 69), with only 1 patient with HVI (0.1%) having a negative CT (ie, none of the 8 a priori CT findings). On bivariate analysis comparing patients with and without HVI, there were significant associations between each of the individual CT scan findings and the presence of HVI. The strongest association was found with the presence of free fluid, with a more than 40-fold increase in the likelihood of HVI (odds ratio [OR], 42.68; 95% CI, 20.48-88.94; P < .001). The presence of free fluid also served as the most effective binary classifier for presence of HVI (area under the receiver operator characteristic curve [AUC], 0.87; 95% CI, 0.83-0.91). There was also an association between a negative CT scan and the absence of HVI (OR, 41.09; 95% CI, 9.01-727.69; P < .001; AUC, 0.68; 95% CI, 0.66-0.70).The prevalence of HVI among patients with an abdominal SBS and negative findings on CT is extremely low, if not zero. The practice of admitting and observing all patients with abdominal SBS should be reconsidered when a high-quality CT scan is negative, which may lead to significant resource and cost savings.
Methadone-Involved Overdose Deaths in the US Before and After Federal Policy Changes Expanding Take-Home Methadone Doses From Opioid Treatment Programs
Authors: Christopher M. Jones, Wilson M. Compton, Beth Han, Grant Baldwin, Nora D. Volkow
Journal: JAMA Psychiatry (2022)

Methadone-Involved Overdose Deaths in the US Before andAfterFederalPolicyChangesExpandingTake-Home Methadone Doses From Opioid Treatment Programs On March 16, 2020, to facilitate access to methadone treatment from opioid treatment programs (OTPs) during the COVID-19 pandemic, the Substance Abuse and Mental Health Services Administration allowed states to request blanket exceptions to provide up to 28 and 14 days of take-home methadone for stable and less stable patients, respectively; this signaled a shift in practice because most patients historically receive methadone daily from OTPs. 1
Complex Interaction of Lithium With Kidney and Bone Health—Reply
Authors: Ole Köhler-Forsberg, Christopher Rohde, Søren Dinesen Østergaard
Journal: JAMA Psychiatry (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Psychiatry HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Psychiatry journal
Safety and Efficacy of Bimekizumab in Patients With Active Psoriatic Arthritis: <scp>Three‐Year</scp> Results From a Phase <scp>IIb</scp> Randomized Controlled Trial and Its <scp>Open‐Label</scp> Extension Study
Authors: Laura C. Coates, Iain B. McInnes, Joseph F. Merola, Richard B. Warren, Arthur Kavanaugh, Alice B. Gottlieb, Laure Gossec, Deepak Assudani, Rajan Bajracharya, Jason Coarse, Barbara Ink, Christopher T. Ritchlin
Journal: Arthritis & Rheumatology (2022)

Objective To assess the long‐term safety, tolerability, and efficacy of bimekizumab in active psoriatic arthritis (PsA). Methods Adult patients with active PsA who completed the double‐ and dose‐blind periods of the BE ACTIVE randomized controlled trial were eligible to enroll in the open‐label extension (OLE) study at week 48, after which patients received 160 mg of bimekizumab every 4 weeks. Safety and efficacy results are presented through 152 weeks. Results At week 152, 161 of 206 patients (78.2%) remained in the study. From weeks 0–152, 184 of 206 patients experienced ≥1 treatment‐emergent adverse event (126.4 per 100 patient‐years). The most frequent events were nasopharyngitis (7.6 per 100 patient‐years), upper respiratory tract infection (6.8 per 100 patient‐years), bronchitis (3.5 per 100 patient‐years), and oral candidiasis (3.5 per 100 patient‐years). Additionally, 47 of 206 patients had mild to moderate localized fungal infections (9.7 per 100 patient‐years), including 24 of 206 patients who had Candida infections (4.6 per 100 patient years) and 19 of 206 patients who had oral candidiasis (3.5 per 100 patient years). Four patients had serious infections (0.7 per 100 patient‐years); there were no reported cases of active tuberculosis, adjudicated major adverse cardiac events, or deaths. Efficacy demonstrated at week 48 was sustained in the OLE study. At week 152, nonresponder imputation analysis showed that 52.9% of patients (69.4% of observed cases) achieved the American College of Rheumatology criteria for 50% improvement, 57.7% (73.8% of observed cases) achieved 100% skin clearance per the Psoriasis Area and Severity Index, and 51.5% (67.5% of observed cases) achieved minimal disease activity. Patients also maintained improvements in pain, physical function, and health‐related quality of life. Conclusion The safety profile of bimekizumab was consistent with previous reports, with no new safety signals identified. Sustained joint and efficacy responses were observed over 3 years.
Targeting p53–MDM2 interaction by small-molecule inhibitors: learning from MDM2 inhibitors in clinical trials
Authors: Haohao Zhu, Hui Gao, Yingying Ji, Qin Zhou, Zhiqiang Du, Lin Tian, Ying Jiang, Kun Yao, Zhenhe Zhou
Journal: Journal of Hematology & Oncology (2022)

Abstract p53, encoded by the tumor suppressor gene TP53, is one of the most important tumor suppressor factors in vivo and can be negatively regulated by MDM2 through p53–MDM2 negative feedback loop. Abnormal p53 can be observed in almost all tumors, mainly including p53 mutation and functional inactivation. Blocking MDM2 to restore p53 function is a hotspot in the development of anticancer candidates. Till now, nine MDM2 inhibitors with different structural types have entered clinical trials. However, no MDM2 inhibitor has been approved for clinical application. This review focused on the discovery, structural modification, preclinical and clinical research of the above compounds from the perspective of medicinal chemistry. Based on this, the possible defects in MDM2 inhibitors in clinical development were analyzed to suggest that the multitarget strategy or targeted degradation strategy based on MDM2 has the potential to reduce the dose-dependent hematological toxicity of MDM2 inhibitors and improve their anti-tumor activity, providing certain guidance for the development of agents targeting the p53–MDM2 interaction.
Health insurance status and cancer stage at diagnosis and survival in the United States
Authors: Jingxuan Zhao, Xuesong Han, Leticia Nogueira, Stacey A. Fedewa, Ahmedin Jemal, Michael T. Halpern, K. Robin Yabroff
Journal: CA A Cancer Journal for Clinicians (2022)

Previous studies using data from the early 2000s demonstrated that patients who were uninsured were more likely to present with late-stage disease and had worse short-term survival after cancer diagnosis in the United States. In this report, the authors provide comprehensive data on the associations of health insurance coverage type with stage at diagnosis and long-term survival in individuals aged 18-64 years who were diagnosed between 2010 and 2013 with 19 common cancers from the National Cancer Database, with survival follow-up through December 31, 2019. Compared with privately insured patients, Medicaid-insured and uninsured patients were significantly more likely to be diagnosed with late-stage (III/IV) cancer for all stageable cancers combined and separately. For all stageable cancers combined and for six cancer sites-prostate, colorectal, non-Hodgkin lymphoma, oral cavity, liver, and esophagus-uninsured patients with Stage I disease had worse survival than privately insured patients with Stage II disease. Patients without private insurance coverage had worse short-term and long-term survival at each stage for all cancers combined; patients who were uninsured had worse stage-specific survival for 12 of 17 stageable cancers and had worse survival for leukemia and brain tumors. Expanding access to comprehensive health insurance coverage is crucial for improving access to cancer care and outcomes, including stage at diagnosis and survival.
Clinical, dermoscopic and histopathological findings in localized human monkeypox: a case from northern Italy
Authors: Carlo A. Maronese, Andrea Beretta, Gianluca Avallone, Francesca L. Boggio, Dario A. Marletta, Giulia Murgia, Marco Cusini, Andrea Gori, Carlo G. Carrera, Alessandra Di Benedetto, Stefano Ramoni, Angelo V. Marzano
Journal: British Journal of Dermatology (2022)

Abstract
Skeletonized Internal Thoracic Artery—Post Hoc Analysis vs Clinical Practice—Reply
Authors: Andre Lamy, Mario Gaudino
Journal: JAMA Cardiology (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Cardiology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Cardiology journal
David Oliver: Covid-19 and the Dunning-Kruger effect
Authors: David Oliver
Journal: BMJ (2022)

1<h3>Abstract</h3> A cornerstone of theoretical neuroscience is the circuit model: a system of equations that captures a hypothesized neural mechanism. Such models are valuable when they give rise to an experimentally observed phenomenon – whether behavioral or in terms of neural activity – and thus can offer insights into neural computation. The operation of these circuits, like all models, critically depends on the choices of model parameters. Historically, the gold standard has been to analytically derive the relationship between model parameters and computational properties. However, this enterprise quickly becomes infeasible as biologically realistic constraints are included into the model increasing its complexity, often resulting in <i>ad hoc</i> approaches to understanding the relationship between model and computation. We bring recent machine learning techniques – the use of deep generative models for probabilistic inference – to bear on this problem, learning distributions of parameters that produce the specified properties of computation. Importantly, the techniques we introduce offer a principled means to understand the implications of model parameter choices on computational properties of interest. We motivate this methodology with a worked example analyzing sensitivity in the stomatogastric ganglion. We then use it to go beyond linear theory of neuron-type input-responsivity in a model of primary visual cortex, gain a mechanistic understanding of rapid task switching in superior colliculus models, and attribute error to connectivity properties in recurrent neural networks solving a simple mathematical task. More generally, this work suggests a departure from realism vs tractability considerations, towards the use of modern machine learning for sophisticated interrogation of biologically relevant models.